Research Affiliates

Sohail Malik, Ph.D.

Dr. Malik studies the regulation of gene expression in eukaryotic cells. Building on the work of Rockefeller’s Robert G. Roeder, research by Dr. Malik and others has contributed to the concept that transcription of messenger RNA genes by RNA polymerase II is a multistep process controlled by the orchestrated action of numerous accessory factors. Of these, the so-called general transcription factors typically suffice for accurate, low-level transcription of naked DNA templates in vitro. Tissue- and gene-specific targeting of these factors to promoter regions of a given gene is achieved via transcriptional activators, which are responsive to various cellular signals and bind to specific DNA sequences that control expression of the gene. Efficient functional coupling of activators and the general transcription machinery is in turn dependent on certain coactivators, foremost among them being the multisubunit Mediator complex. Working in Dr. Roeder’s group, Dr. Malik was among the first to isolate the Mediator. He and his colleagues then went on to characterize it extensively, both structurally and functionally.

In recent work, Dr. Malik and his colleagues have used nuclear receptors, specifically HNF-4, to probe transcriptional mechanisms. HNF-4, an important regulator of both fetal development and organogenesis and adult physiology, is primarily expressed in the liver and intestine in adult animals. Overall, evidence from Dr. Malik’s group, as well as from many other laboratories, increasingly highlights the central role of Mediator in unifying the expression programs of individual genes. It is likely that Mediator functions as an “integrative hub” that assimilates the multiple signals feeding into the gene and modulates the appropriate transcriptional response.